Organ Failure and Nutrition
There are four critical organ systems that are especially likely to fail in aging and critical illness. They are the cardiovascular, central nervous, musculoskeletal and immune systems.
Relationship of Malnutrition to Mitochondrial Function
Protein-calorie malnutrition contributes to both skeletal and cardiac.sup.1 muscle dysfunction in patients with cardiac failure. Muscle is composed of water, minerals, nitrogen and glycogen.sup.2,3. Feeding wasted individuals results in a gain of the multiple elements in lean tissue.sup.4 including potassium. Body potassium, has been used as an index of body cell mass.sup.5, the metabolically active component of the lean tissue. In contrast to body nitrogen, body potassium responds rapidly to feeding by both oral and intravenous routes.sup.6,7,8,9,10. It has been shown that in malnutrition there is a change in muscle membrane potential resulting in reduced intracellular ionic potassium. The reduced cellular potassium cannot be simply corrected by giving potassium but requires restitution of nutrition. The above mentioned observations suggest that cell ion uptake, an energy dependent process, occurs earlier than protein synthesis during nutritional support. This concept has received experimental support by two studies using .sup.31 P-NMR which showed that malnutrition was associated with a reduced rate of oxidative phosphorylation, suggesting a mitochondrial abnormality.sup.11,12.
Cell energetics are also important for muscle activity and it has been shown.sup.13,14,15,16,17,18,19,20,21,22 that skeletal muscle function, including that of the diaphragm, can be rapidly altered by nutrient deprivation and restored by refeeding. Also the changes in muscle function are specific to alterations in the nutritional status and are not influenced by sepsis, trauma, renal failure and steroid administration.sup.15,17. Christie and Hill indicated that nutritional support improves muscle, including diaphragmatic function before any increase in body protein or body mass.sup.20. Windsor and Hill.sup.21 demonstrated that the functional effects of nutrition are more important than subnormal body protein as an index of surgical risk. Hanning and her colleagues.sup.22 demonstrated the ability of stimulated muscle function as demonstrated by a slow relaxation rate and an altered force-frequency curve to predict the ability of patients with cystic fibrosis to grow as an outcome measure. In contrast, body composition, protein biochemistry, muscle power on an ergometer or use of supplements did not predict growth potential. Among the macronutrients, Castenada et al.sup.23 have shown that protein deficiency can profoundly alter muscle function even when energy intake is sufficient to meet requirements.
The data given above indicate that it is critical to correct protein-calorie malnutrition, with an emphasis on protein repletion, in order to obtain the maximum functional benefits of administering skeletal muscle specific micronutrients. Current diet supplementing strategies for correcting protein-calorie malnutrition focus on giving supplements of protein and energy (carbohydrates and fats). No supplement to date has addressed the cascading series of metabolic abnormalities that can lead to mitochondrial dysfunction.